Improved palliative management of osseous metastatic lesions has resulted in marked increase both in patient survival times and in the incidence of pathologic fractures. The assessment and treatment of established osseous metastases is thus an increasingly important aspect of the clinical management of cancer patients. Unfortunately, only the most qualitative of clinical guidelines are available for assessing fracture risk associated with metastatic lesions. Moreover, guidelines have not been developed for regions such as the proximal femur and spine where osseous metastases are most common. During the previous funding period, we have continued the development of biomechanical predictors of fracture risk associated with diaphyseal lesions and extended our combined experimental and analytical approaches to metastases of the proximal femur and spine. Among other findings, these studies show clearly that current clinical guidelines for prophylactic stabilization of metastatic lesions are inadequate and must be revised to reflect a more appropriate weighting of pain, functional requirements and biomechanical factors. To begin to address these issues, we also developed and applied new clinical assessment procedures based on flexural rigidity estimates and three-dimensional reconstructions of Quantitative Computed Tomography (QCT) scans through the site of the lesion. We also initiated a pilot study of patients with metastases to the femur and spine secondary to breast or prostate cancer being treated by the Joint Center for Radiotherapy. In the proposed competitive renewal, we will focus on developing more reliable fracture risk predictors for the proximal femur and spine and will extend our pilot study to a representative sample of patients being treated for metastatic lesions of the femur and spine. Under aim 1, we will complete our biomechanical studies of diaphyseal lesions and extend our analyses of strength reductions associated with metastases to the proximal femur. Special attention will be given to the validation of our fracture risk predictors using in-vitro tests of cadaver bones with either simulated or actual metastatic lesions. We will also explore the use of three-dimensional reconstructions of QCT data and the generation of patient-specific finite element models for femoral fracture risk prediction. Under aim 2, we will determine the sensitivity of QCT measures of lesion geometries and density changes in the spine and use these to resolve contradictions regarding the strength reductions associated with lesions which penetrate the vertebral cortex. Under aim 3, we will use QCT scans, biomechanical analyses and psychometric assessments of pain and function to evaluate the response of osseous metastases to standard radiotherapy treatment protocols used at the Joint Centers for Radiation. Therapy for metastatic lesions of the proximal femur and spine. We expect these data to provide more comprehensive and appropriately weighted assessment tools which include not only biomechanical predictors of fracture risk, but also clinical factors which are important to the management of these patients. An additional outcome will be enhanced insight into the temporal course and structural efficiency of the osseous response to radiation therapy. Baseline data from this pilot study will then allow us to make power calculations necessary to design prospective trials for comparing different treatment options for painful osseous metastases.